| First Author | Beilke JN | Year | 2005 |
| Journal | Nat Med | Volume | 11 |
| Issue | 10 | Pages | 1059-65 |
| PubMed ID | 16155578 | Mgi Jnum | J:101693 |
| Mgi Id | MGI:3604828 | Doi | 10.1038/nm1296 |
| Citation | Beilke JN, et al. (2005) NK cells promote islet allograft tolerance via a perforin-dependent mechanism. Nat Med 11(10):1059-65 |
| abstractText | Although major histocompatibility complex (MHC) class II-restricted CD4 T cells are well appreciated for their contribution to peripheral tolerance to tissue allografts, little is known regarding MHC class I-dependent reactivity in this process. Here we show a crucial role for host MHC class I-dependent NK cell reactivity for allograft tolerance in mice induced through either costimulation blockade using CD154-specific antibody therapy or by targeting LFA-1 (also known as CD11a). Tolerance induction absolutely required host expression of MHC class I, but was independent of CD8 T cell-dependent immunity. Rather, tolerance required innate immunity involving NK1.1(+) cells, but was independent of CD1d-restricted NKT cells. Therefore, NK cells seem to be generally required for induction of tolerance to islet allografts. Additional studies indicate that CD154-specific antibody-induced allograft tolerance is perforin dependent. Notably, NK cells that are perforin competent are sufficient to restore allograft tolerance in perforin-deficient recipients. Together, these results show an obligatory role for NK cells, through perforin, for induction of tolerance to islet allografts. |
